ID SPRE1_HUMAN Reviewed; 444 AA. AC Q7Z699; B2RPJ8; Q05D53; Q8N256; DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot. DT 04-JAN-2005, sequence version 2. DT 18-SEP-2013, entry version 93. DE RecName: Full=Sprouty-related, EVH1 domain-containing protein 1; DE Short=Spred-1; DE Short=hSpred1; GN Name=SPRED1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH SPRED2. RC TISSUE=Glioblastoma; RX PubMed=15683364; DOI=10.1042/BJ20041284; RA King J.A.J., Straffon A.F.L., D'Abaco G.M., Poon C.L.C., I S.T.T., RA Smith C.M., Buchert M., Corcoran N.M., Hall N.E., Callus B.A., RA Sarcevic B., Martin D., Lock P., Hovens C.M.; RT "Distinct requirements for the Sprouty domain for functional activity RT of Spred proteins."; RL Biochem. J. 388:445-454(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP TISSUE SPECIFICITY. RX PubMed=15580519; DOI=10.1007/s00418-004-0725-6; RA Engelhardt C.M., Bundschu K., Messerschmitt M., Renne T., Walter U., RA Reinhard M., Schuh K.; RT "Expression and subcellular localization of Spred proteins in mouse RT and human tissues."; RL Histochem. Cell Biol. 122:527-538(2004). RN [6] RP INTERACTION WITH CAV1, AND SUBCELLULAR LOCATION. RX PubMed=16115197; DOI=10.1111/j.1365-2443.2005.00886.x; RA Nonami A., Taketomi T., Kimura A., Saeki K., Takaki H., Sanada T., RA Taniguchi K., Harada M., Kato R., Yoshimura A.; RT "The Sprouty-related protein, Spred-1, localizes in a lipid RT raft/caveola and inhibits ERK activation in collaboration with RT caveolin-1."; RL Genes Cells 10:887-895(2005). RN [7] RP INVOLVEMENT IN NFLS. RX PubMed=17704776; DOI=10.1038/ng2113; RA Brems H., Chmara M., Sahbatou M., Denayer E., Taniguchi K., Kato R., RA Somers R., Messiaen L., De Schepper S., Fryns J.-P., Cools J., RA Marynen P., Thomas G., Yoshimura A., Legius E.; RT "Germline loss-of-function mutations in SPRED1 cause a RT neurofibromatosis 1-like phenotype."; RL Nat. Genet. 39:1120-1126(2007). RN [8] RP VARIANT NFLS ASP-44. RX PubMed=19443465; DOI=10.1136/jmg.2008.065474; RA Spurlock G., Bennett E., Chuzhanova N., Thomas N., Jim H.P., Side L., RA Davies S., Haan E., Kerr B., Huson S.M., Upadhyaya M.; RT "SPRED1 mutations (Legius syndrome): another clinically useful RT genotype for dissecting the neurofibromatosis type 1 phenotype."; RL J. Med. Genet. 46:431-437(2009). RN [9] RP VARIANT NFLS ASP-44. RX PubMed=20108422; RA Jim H.P., Upadhyaya M.; RT "Novel human pathological mutations. Gene symbol: SPRED1. Disease: RT Legius syndrome."; RL Hum. Genet. 127:112-112(2010). RN [10] RP VARIANT NFLS CYS-31. RX PubMed=21089071; DOI=10.1002/humu.21404; RA Denayer E., Chmara M., Brems H., Kievit A.M., van Bever Y., RA Van den Ouweland A.M., Van Minkelen R., de Goede-Bolder A., RA Oostenbrink R., Lakeman P., Beert E., Ishizaki T., Mori T., RA Keymolen K., Van den Ende J., Mangold E., Peltonen S., Brice G., RA Rankin J., Van Spaendonck-Zwarts K.Y., Yoshimura A., Legius E.; RT "Legius syndrome in fourteen families."; RL Hum. Mutat. 32:E1985-E1998(2011). CC -!- FUNCTION: Tyrosine kinase substrate that inhibits growth-factor- CC mediated activation of MAP kinase. Negatively regulates CC hematopoiesis of bone marrow (By similarity). CC -!- SUBUNIT: Interacts with Ras. Interacts with TAOK2 and TESK1 (By CC similarity). Homodimer and heterodimer. Interacts with CAV1. Able CC to interact with SPRED2 to form heterodimers. CC -!- INTERACTION: CC P62136:PPP1CA; NbExp=3; IntAct=EBI-5235340, EBI-357253; CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein. CC Membrane, caveola; Peripheral membrane protein. Nucleus. CC Note=Localized in cholesterol-rich membrane raft/caveola CC fractions. CC -!- TISSUE SPECIFICITY: Weakly expressed in embryonic cell line CC HEK293. CC -!- PTM: Phosphorylated on tyrosine (By similarity). CC -!- DISEASE: Neurofibromatosis 1-like syndrome (NFLS) [MIM:611431]: A CC disorder characterized mainly by cafe au lait macules without CC neurofibromas or other tumor manifestations of neurofibromatosis CC type 1, axillary freckling, and macrocephaly. Additional clinical CC manifestations include Noonan-like facial dysmorphism, lipomas, CC learning disabilities and attention deficit-hyperactivity. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Contains 1 KBD domain. CC -!- SIMILARITY: Contains 1 SPR (sprouty) domain. CC -!- SIMILARITY: Contains 1 WH1 domain. CC -!- SEQUENCE CAUTION: CC Sequence=AAH18015.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY299089; AAP59414.1; -; mRNA. DR EMBL; AK091222; BAC03614.1; -; mRNA. DR EMBL; CH471125; EAW92368.1; -; Genomic_DNA. DR EMBL; BC018015; AAH18015.1; ALT_SEQ; mRNA. DR EMBL; BC137480; AAI37481.1; -; mRNA. DR EMBL; BC137481; AAI37482.1; -; mRNA. DR IPI; IPI00166291; -. DR RefSeq; NP_689807.1; NM_152594.2. DR UniGene; Hs.525781; -. DR PDB; 3SYX; X-ray; 2.45 A; A=13-131. DR PDBsum; 3SYX; -. DR ProteinModelPortal; Q7Z699; -. DR SMR; Q7Z699; 13-127. DR IntAct; Q7Z699; 2. DR MINT; MINT-1198540; -. DR STRING; 9606.ENSP00000299084; -. DR PhosphoSite; Q7Z699; -. DR DMDM; 57013078; -. DR PaxDb; Q7Z699; -. DR PRIDE; Q7Z699; -. DR Ensembl; ENST00000299084; ENSP00000299084; ENSG00000166068. DR GeneID; 161742; -. DR KEGG; hsa:161742; -. DR UCSC; uc001zka.4; human. DR CTD; 161742; -. DR GeneCards; GC15P038545; -. DR HGNC; HGNC:20249; SPRED1. DR HPA; HPA042193; -. DR MIM; 609291; gene. DR MIM; 611431; phenotype. DR neXtProt; NX_Q7Z699; -. DR Orphanet; 137605; Legius syndrome. DR PharmGKB; PA134897382; -. DR eggNOG; NOG277322; -. DR HOGENOM; HOG000220886; -. DR HOVERGEN; HBG057556; -. DR InParanoid; Q7Z699; -. DR KO; K04703; -. DR OMA; CVTVFKV; -. DR OrthoDB; EOG40CHH0; -. DR PhylomeDB; Q7Z699; -. DR ChiTaRS; SPRED1; human. DR GeneWiki; SPRED1; -. DR GenomeRNAi; 161742; -. DR NextBio; 88102; -. DR ArrayExpress; Q7Z699; -. DR Bgee; Q7Z699; -. DR CleanEx; HS_SPRED1; -. DR Genevestigator; Q7Z699; -. DR GO; GO:0005901; C:caveola; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0019902; F:phosphatase binding; IDA:UniProtKB. DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; ISS:BHF-UCL. DR GO; GO:0005173; F:stem cell factor receptor binding; ISS:UniProtKB. DR GO; GO:0000188; P:inactivation of MAPK activity; ISS:UniProtKB. DR GO; GO:0007275; P:multicellular organismal development; IEA:InterPro. DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; IMP:BHF-UCL. DR GO; GO:0010923; P:negative regulation of phosphatase activity; IDA:UniProtKB. DR GO; GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; ISS:BHF-UCL. DR GO; GO:0090311; P:regulation of protein deacetylation; ISS:BHF-UCL. DR Gene3D; 2.30.29.30; -; 1. DR InterPro; IPR000697; EVH1. DR InterPro; IPR023337; KBD. DR InterPro; IPR011993; PH_like_dom. DR InterPro; IPR007875; Sprouty. DR Pfam; PF05210; Sprouty; 1. DR Pfam; PF00568; WH1; 1. DR PROSITE; PS51488; KBD; 1. DR PROSITE; PS51227; SPR; 1. DR PROSITE; PS50229; WH1; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Complete proteome; Disease mutation; KW Membrane; Nucleus; Phosphoprotein; Reference proteome. FT CHAIN 1 444 Sprouty-related, EVH1 domain-containing FT protein 1. FT /FTId=PRO_0000076907. FT DOMAIN 6 123 WH1. FT DOMAIN 233 285 KBD. FT DOMAIN 334 442 SPR. FT COMPBIAS 147 150 Poly-Ser. FT MOD_RES 238 238 Phosphoserine (By similarity). FT VARIANT 31 31 W -> C (in NFLS). FT /FTId=VAR_064827. FT VARIANT 44 44 V -> D (in NFLS). FT /FTId=VAR_064828. FT CONFLICT 6 7 AT -> GL (in Ref. 1; AAP59414). FT STRAND 13 24 FT STRAND 26 29 FT STRAND 31 37 FT STRAND 40 51 FT STRAND 54 64 FT TURN 65 67 FT STRAND 70 75 FT STRAND 81 86 FT STRAND 89 94 FT STRAND 97 105 FT HELIX 106 121 FT HELIX 122 124 SQ SEQUENCE 444 AA; 50477 MW; 6FFDECCE590DB311 CRC64; MSEETATSDN DNSYARVRAV VMTRDDSSGG WLPLGGSGLS SVTVFKVPHQ EENGCADFFI RGERLRDKMV VLECMLKKDL IYNKVTPTFH HWKIDDKKFG LTFQSPADAR AFDRGIRRAI EDISQGCPES KNEAEGADDL QANEEDSSSS LVKDHLFQQE TVVTSEPYRS SNIRPSPFED LNARRVYMQS QANQITFGQP GLDIQSRSME YVQRQISKEC GSLKSQNRVP LKSIRHVSFQ DEDEIVRINP RDILIRRYAD YRHPDMWKND LERDDADSSI QFSKPDSKKS DYLYSCGDET KLSSPKDSVV FKTQPSSLKI KKSKRRKEDG ERSRCVYCQE RFNHEENVRG KCQDAPDPIK RCIYQVSCML CAESMLYHCM SDSEGDFSDP CSCDTSDDKF CLRWLALVAL SFIVPCMCCY VPLRMCHRCG EACGCCGGKH KAAG //